• Open Access

Myoblasts from affected and non-affected FSHD muscles exhibit morphological differentiation defects

Authors

  • Marietta Barro,

    1. INSERM, ERI25, Montpellier, France
    2. Université Montpellier1, UFR Médecine, Montpellier, France
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  • Gilles Carnac,

    1. INSERM, ERI25, Montpellier, France
    2. Université Montpellier1, UFR Médecine, Montpellier, France
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  • Sébastien Flavier,

    1. INSERM, ERI25, Montpellier, France
    2. Université Montpellier1, UFR Médecine, Montpellier, France
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  • Jacques Mercier,

    1. INSERM, ERI25, Montpellier, France
    2. Université Montpellier1, UFR Médecine, Montpellier, France
    3. CHU de Montpellier, Service de Physiologie Clinique, Hôpital A. de Villeneuve, Montpellier, France
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  • Yegor Vassetzky,

    1. CNRS, UMR8126 CNRS, Université Paris-Sud 11, Institut de Cancérologie Gustave-Roussy, Villejuif, France
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  • Dalila Laoudj-Chenivesse

    Corresponding author
    1. INSERM, ERI25, Montpellier, France
    2. Université Montpellier1, UFR Médecine, Montpellier, France
      Correspondence to: D. Laoudj-Chenivesse, INSERM ERI 25, Bâtiment Crastes de Paulet, Hôpital A. de Villeneuve, 34295 Montpellier Cedex 5, France.
      Tel.: +(33) 4 67 41 52 26
      Fax: +(33) 4 67 41 52 31
      E-mail: dalila.laoudj-chenivesse@inserm.fr
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Correspondence to: D. Laoudj-Chenivesse, INSERM ERI 25, Bâtiment Crastes de Paulet, Hôpital A. de Villeneuve, 34295 Montpellier Cedex 5, France.
Tel.: +(33) 4 67 41 52 26
Fax: +(33) 4 67 41 52 31
E-mail: dalila.laoudj-chenivesse@inserm.fr

Abstract

Facioscapulohumeral dystrophy (FSHD) is a muscular hereditary disease with a prevalence of 1 in 20,000 caused by a partial deletion of a subtelomeric repeat array on chromosome 4q. However, very little is known about the pathogenesis as well as the molecular and biochemical changes linked to the progressive muscle degeneration observed in these patients. Several studies have investigated possible pathophysiological pathways in FSHD myoblasts and mature muscle cells but some of these reports were apparently in contradiction. The discrepancy between these studies may be explained by differences between the sources of myoblasts. Therefore, we decided to thoroughly analyze affected and unaffected muscles from patients with FSHD in terms of vulnerability to oxidative stress, differentiation capacity and morphological abnormalities. We have established a panel of primary myoblast cell cultures from patients affected with FSHD and matched healthy individuals. Our results show that primary myoblasts are more susceptible to an induced oxidative stress than control myoblasts. Moreover, we demonstrate that both types of FSHD primary myoblasts differentiate into multi-nucleated myotubes, which present morphological abnormalities. Whereas control myoblasts fuse to form branched myotubes with aligned nuclei, FSHD myoblasts fuse to form either thin and branched myotubes with aligned nuclei or large myotubes with random nuclei distribution. In conclusion, we postulate that these abnormalities could be responsible for muscle weakness in patients with FSHD and provide an important marker for FSHD myoblasts.

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